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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2022-03-07 02:51:48 UTC
HMDB IDHMDB0014958
Secondary Accession Numbers
  • HMDB14958
Metabolite Identification
Common NameTadalafil
DescriptionTadalafil is an orally adminstered drug used to treat male erectile dysfunction (impotence). It is marketed worldwide under the brand name Cialis. It is a phosphodiesterase 5 (PDE5) inhibitor. Tadalafil's distinguishing pharmacologic feature is its longer half-life (17.5 hours) compared with Viagra and Levitra (4-5 hours). This longer half-life results in a longer duration of action and is, in part, responsible for the Cialis nickname of the 'weekend pill.' This longer half-life also is the basis of current investigation for tadalafil's use in pulmonary arterial hypertension as a once-daily therapy. [Wikipedia ]
Structure
Data?1582753242
Synonyms
ValueSource
(6R,12AR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-(methylenedioxy)phenyl) pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dioneChEBI
(6R-trans)-6-(1,3-Benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino(1',2':1,6)pyrido(3,4-b)indole-1,4-dioneChEBI
6-BENZO[1,3]dioxol-5-yl-2-methyl-2,3,6,7,12,12a-hexahydro-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dioneChEBI
AdcircaChEBI
CialisChEBI
ZalutiaKegg
ICOS 351HMDB
TadanafilHMDB
351, ICHMDB
Chemical FormulaC22H19N3O4
Average Molecular Weight389.404
Monoisotopic Molecular Weight389.137556111
IUPAC Name(2R,8R)-2-(2H-1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.0³,⁸.0¹¹,¹⁶]heptadeca-1(10),11,13,15-tetraene-4,7-dione
Traditional Nametadalafil
CAS Registry Number171596-29-5
SMILES
[H][C@]12CC3=C(NC4=CC=CC=C34)[C@H](N1C(=O)CN(C)C2=O)C1=CC2=C(OCO2)C=C1
InChI Identifier
InChI=1S/C22H19N3O4/c1-24-10-19(26)25-16(22(24)27)9-14-13-4-2-3-5-15(13)23-20(14)21(25)12-6-7-17-18(8-12)29-11-28-17/h2-8,16,21,23H,9-11H2,1H3/t16-,21-/m1/s1
InChI KeyWOXKDUGGOYFFRN-IIBYNOLFSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as beta carbolines. Beta carbolines are compounds containing a 9H-pyrido[3,4-b]indole moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassPyridoindoles
Direct ParentBeta carbolines
Alternative Parents
Substituents
  • Beta-carboline
  • Alpha-amino acid or derivatives
  • 3-alkylindole
  • Benzodioxole
  • Indole
  • 2,5-dioxopiperazine
  • Dioxopiperazine
  • N-methylpiperazine
  • N-alkylpiperazine
  • Benzenoid
  • Piperazine
  • 1,4-diazinane
  • Tertiary carboxylic acid amide
  • Pyrrole
  • Heteroaromatic compound
  • Carboxamide group
  • Lactam
  • Acetal
  • Carboxylic acid derivative
  • Oxacycle
  • Azacycle
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point301 - 302 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.25 g/LNot Available
LogP1.7Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM189.430932474
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.25 g/LALOGPS
logP2.36ALOGPS
logP1.64ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.17ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area74.87 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity104.08 m³·mol⁻¹ChemAxon
Polarizability40.92 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+187.81231661259
DarkChem[M-H]-186.65231661259
DeepCCS[M-2H]-222.84130932474
DeepCCS[M+Na]+198.26630932474
AllCCS[M+H]+192.732859911
AllCCS[M+H-H2O]+189.832859911
AllCCS[M+NH4]+195.332859911
AllCCS[M+Na]+196.032859911
AllCCS[M-H]-197.532859911
AllCCS[M+Na-2H]-197.132859911
AllCCS[M+HCOO]-196.832859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
Tadalafil[H][C@]12CC3=C(NC4=CC=CC=C34)[C@H](N1C(=O)CN(C)C2=O)C1=CC2=C(OCO2)C=C15155.5Standard polar33892256
Tadalafil[H][C@]12CC3=C(NC4=CC=CC=C34)[C@H](N1C(=O)CN(C)C2=O)C1=CC2=C(OCO2)C=C13785.8Standard non polar33892256
Tadalafil[H][C@]12CC3=C(NC4=CC=CC=C34)[C@H](N1C(=O)CN(C)C2=O)C1=CC2=C(OCO2)C=C13900.4Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Tadalafil,1TMS,isomer #1CN1CC(=O)N2[C@H](CC3=C([C@H]2C2=CC=C4OCOC4=C2)N([Si](C)(C)C)C2=CC=CC=C32)C1=O3619.5Semi standard non polar33892256
Tadalafil,1TMS,isomer #1CN1CC(=O)N2[C@H](CC3=C([C@H]2C2=CC=C4OCOC4=C2)N([Si](C)(C)C)C2=CC=CC=C32)C1=O3613.8Standard non polar33892256
Tadalafil,1TMS,isomer #1CN1CC(=O)N2[C@H](CC3=C([C@H]2C2=CC=C4OCOC4=C2)N([Si](C)(C)C)C2=CC=CC=C32)C1=O4812.1Standard polar33892256
Tadalafil,1TBDMS,isomer #1CN1CC(=O)N2[C@H](CC3=C([C@H]2C2=CC=C4OCOC4=C2)N([Si](C)(C)C(C)(C)C)C2=CC=CC=C32)C1=O3799.5Semi standard non polar33892256
Tadalafil,1TBDMS,isomer #1CN1CC(=O)N2[C@H](CC3=C([C@H]2C2=CC=C4OCOC4=C2)N([Si](C)(C)C(C)(C)C)C2=CC=CC=C32)C1=O3866.6Standard non polar33892256
Tadalafil,1TBDMS,isomer #1CN1CC(=O)N2[C@H](CC3=C([C@H]2C2=CC=C4OCOC4=C2)N([Si](C)(C)C(C)(C)C)C2=CC=CC=C32)C1=O4838.0Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Tadalafil GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-3097000000-803ff86b2ce502e2bc832017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Tadalafil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Tadalafil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil LC-ESI-qTof , Positive-QTOFsplash10-02t9-2890000000-0be3708ad44a8a467cc52017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil Linear Ion Trap , negative-QTOFsplash10-03di-0090000000-c52485d22b5893fc60a22017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil Linear Ion Trap , negative-QTOFsplash10-03di-0090000000-2f6ad2194cd2932b07612017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil Linear Ion Trap , positive-QTOFsplash10-0i0r-0291000000-a4ae40141abccfc867102017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil Linear Ion Trap , positive-QTOFsplash10-0j59-0290000000-86095fe2d98833db9d0b2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil Linear Ion Trap , positive-QTOFsplash10-0uy0-0429200000-641774545afc893151342017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil Linear Ion Trap , positive-QTOFsplash10-0uy0-0429200000-f223c860e93cceeeacd82017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil , positive-QTOFsplash10-014i-0292000000-0563bdd5b0be8c1cfa472017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil , positive-QTOFsplash10-02t9-2890000000-0be3708ad44a8a467cc52017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 35V, Positive-QTOFsplash10-014i-0391000000-2d53d99ea189cbcf20bf2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 10V, Positive-QTOFsplash10-0f6x-0009000000-bea170f3de4098be75e02021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 40V, Positive-QTOFsplash10-001i-0191000000-b10465a3e1f68719ab502021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 20V, Positive-QTOFsplash10-0udi-0019000000-989b326813e322333fa52021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 20V, Negative-QTOFsplash10-004i-0119000000-28b2b617eb618183d5c82021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 40V, Negative-QTOFsplash10-001i-0791000000-5534e9b8d8ed5169e6232021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 10V, Negative-QTOFsplash10-000i-0009000000-844cd3bb8e0273b1cadd2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Tadalafil 35V, Negative-QTOFsplash10-03di-0091000000-612762fb281177438c8e2021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 10V, Positive-QTOFsplash10-0006-0009000000-cfa5abcf4ec76ea41d682016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 20V, Positive-QTOFsplash10-0006-1019000000-59cc81b34404c6ecd1672016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 40V, Positive-QTOFsplash10-0006-0291000000-20d1a51d47c7345d57422016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 10V, Negative-QTOFsplash10-000i-2009000000-721840625f2b26eb19a72016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 20V, Negative-QTOFsplash10-052r-4019000000-5dff72997668963ef3192016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 40V, Negative-QTOFsplash10-01pc-2191000000-f8bd70ef77444b35f09b2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 10V, Positive-QTOFsplash10-0006-0029000000-5ec0e4346a39de6e65822021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Tadalafil 20V, Positive-QTOFsplash10-0006-0009000000-565961b51e5cb53f55d42021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00820 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00820 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00820
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID99301
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTadalafil
METLIN IDNot Available
PubChem Compound110635
PDB IDCIA
ChEBI ID71940
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Guazzi M, Samaja M: The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development. Curr Med Chem. 2007;14(20):2181-91. [PubMed:17691956 ]
  2. Naeije R, Huez S: Expert opinion on available options treating pulmonary arterial hypertension. Expert Opin Pharmacother. 2007 Oct;8(14):2247-65. [PubMed:17927481 ]
  3. Burnett AL: Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health. J Androl. 2008 Jan-Feb;29(1):3-14. Epub 2007 Oct 17. [PubMed:17942972 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.
Gene Name:
PDE5A
Uniprot ID:
O76074
Molecular weight:
99984.14
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Curran M, Keating G: Tadalafil. Drugs. 2003;63(20):2203-12; discussion 2213-4. [PubMed:14498756 ]
  3. Eardley I, Cartledge J: Tadalafil (Cialis) for men with erectile dysfunction. Int J Clin Pract. 2002 May;56(4):300-4. [PubMed:12074215 ]
  4. Montorsi F, Salonia A, Deho' F, Cestari A, Guazzoni G, Rigatti P, Stief C: Pharmacological management of erectile dysfunction. BJU Int. 2003 Mar;91(5):446-54. [PubMed:12603396 ]
  5. Rotella DP: Tadalafil Lilly ICOS. Curr Opin Investig Drugs. 2003 Jan;4(1):60-5. [PubMed:12625031 ]
  6. Roumeguere T, Sternon J, Schulman CC: [Erectile dysfunction and phosphodiesterase type 5 inhibitors]. Rev Med Brux. 2003 Jun;24(3):169-75. [PubMed:12891884 ]
  7. Zoraghi R, Francis SH, Corbin JD: Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors. Biochemistry. 2007 Nov 27;46(47):13554-63. Epub 2007 Nov 3. [PubMed:17979301 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in catalytic activity
Specific function:
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively.
Gene Name:
PDE11A
Uniprot ID:
Q9HCR9
Molecular weight:
55699.16
References
  1. Weeks JL 2nd, Corbin JD, Francis SH: Interactions between cyclic nucleotide phosphodiesterase 11 catalytic site and substrates or tadalafil and role of a critical Gln-869 hydrogen bond. J Pharmacol Exp Ther. 2009 Oct;331(1):133-41. doi: 10.1124/jpet.109.156935. Epub 2009 Jul 29. [PubMed:19641165 ]
  2. Weeks JL 2nd, Zoraghi R, Francis SH, Corbin JD: N-Terminal domain of phosphodiesterase-11A4 (PDE11A4) decreases affinity of the catalytic site for substrates and tadalafil, and is involved in oligomerization. Biochemistry. 2007 Sep 11;46(36):10353-64. Epub 2007 Aug 16. [PubMed:17696499 ]